Dr. F. Ivy Carroll has designed a series of 3-phenyltropane analogs that potently and selectively bind to the same site as cocaine on the dopamine transporter (DAT). Forty-seven of these analogs have IC50 values at the DAT of less than 10 nM and selectively for the DAT >100 times their selectively for the serotonin and norepinephrine transporters. The goal is to develop behavioral information on those 47 compounds to allow detailed work on four and selection of one for clinical evaluation against cocaine abuse. The specific aims of this grant follow from application: (a) no deaths or conclusions at 100 mg/kg, (b) locomoter stimulation equal to or less than that produced by cocaine, (c) slower onset and longer duration of reaction than that produced by cocaine, (d) generalization in cocaine-trained rats, and (3) activity by the oral route. Information has already been generated for 19 of the 47 DAT selective 3-phenyltropanes and partial information exists for all, leaving 17 compounds which remain to be evaluated. The specific aims for this grant are (1) to evaluate 17 DAT-selective compounds for death or convulsions at 100 mg/kg i.p. in mice, (2) to determine locomoter activity dose-effect curves in mice for compounds that are clean in (1), (2) equal to or less than that caused by cocaine, and (4) to determine oral activity for compounds that meet the other selection criteria. These specific aims will be accomplished in the first 5 months of the grant and will allow the selection of the four best compounds from the initial 47. The last specific aim (5) is to evaluate the best four for tolerance or sensitization in locomoter activity.